245 research outputs found
Poroelastic indentation of mechanically confined hydrogel layers
We report on the poroelastic indentation response of hydrogel thin films
geometrically confined within contacts with rigid spherical probes of radii in
the millimeter range. Poly(PEGMA) (poly(ethylene glycol)) methyl ether
methacrylate), poly(DMA) (dimethylacrylamide) and poly(NIPAM)
(\textit{N}-isopropylacrylamide) gel films with thickness less than 15 m
were grafted onto glass substrates using a thiol-ene click chemistry route.
Changes in the indentation depth under constant applied load were monitored
over time as a function of the film thickness and the radius of curvature of
the probe using an interferometric method. In addition, shear properties of the
indented films were measured using a lateral contact method. In the case of
poly(PEGMA) films, we show that poroelastic indentation behavior is adequately
described within the framework of an approximate contact model derived within
the limits of confined contact geometries. This model provides simple scaling
laws for the characteristic poroelastic time and the equilibrium indentation
depth. Conversely, deviations from this model are evidenced for poly(DMA) and
poly(NIPAM) films. From lateral contact experiments, these deviations are found
to result from strong changes in the shear properties as a result of glass
transition (poly(DMA)) or phase separation (poly(NIPAM)) phenomena induced by
the drainage of the confined films squeezed between the rigid substrates
Microfluidic rheology of soft colloids above and below jamming
The rheology near jamming of a suspension of soft colloidal spheres is
studied using a custom microfluidic rheometer that provides stress versus
strain rate over many decades. We find non-Newtonian behavior below the jamming
concentration and yield stress behavior above it. The data may be collapsed
onto two branches with critical scaling exponents that agree with expectations
based on Hertzian contacts and viscous drag. These results support the
conclusion that jamming is similar to a critical phase transition, but with
interaction-dependent exponents.Comment: 4 pages, experimen
Bouncing or sticky droplets: impalement transitions on superhydrophobic micropatterned surfaces
When a liquid drops impinges a hydrophobic rough surface it can either bounce
off the surface (fakir droplets) or be impaled and strongly stuck on it (Wenzel
droplets). The analysis of drop impact and quasi static ''loading'' experiments
on model microfabricated surfaces allows to clearly identify the forces
hindering the impalement transitions. A simple semi-quantitative model is
proposed to account for the observed relation between the surface topography
and the robustness of fakir non-wetting states. Motivated by potential
applications in microfluidics and in the fabrication of self cleaning surfaces,
we finally propose some guidelines to design robust superhydrophobic surfaces.Comment: 7 pages, 5 figure
Multifocal Aggressive Squamous Cell Carcinomas Induced by Prolonged Voriconazole Therapy: A Case Report
Voriconazole is a treatment for severe fungal infections. Prolonged voriconazole therapy may induce skin reactions, with 1% of severe photosensitivity accidents. Recently the imputability of voriconazole in skin carcinogenesis has been suggested. This report concerns a 55-year-old man suffering from pulmonary aspergillosis who presented a phototoxic reaction a few months after introduction of voriconazole, followed by multiple squamous cell carcinomas of sun-exposed skin areas. After voriconazole discontinuation, no new carcinoma was observed. The detection of EBV and HPV in skin lesions was negative. Exploration of gene mutations involved in skin carcinogenesis showed two variants of the MICR gene. The occurrence of multiple, recurrent, aggressive squamous cell carcinomas is rare with voriconazole, but its imputability is strongly suggested. A plausible hypothesis is that several factors including voriconazole uptake, immunosuppression, and genetic background could explain the phenotype of fast-developing skin carcinomas. Voriconazole therapy should be accompanied by stringent photoprotection and skin monitoring
Biochemical Diagnosis of a Fatal Case of Günther’s Disease in a Newborn with Hydrops Foetalis
Peer Reviewe
Genome-Wide Identification of Small RNAs in the Opportunistic Pathogen Enterococcus faecalis V583
Small RNA molecules (sRNAs) are key mediators of virulence and stress inducible gene expressions in some pathogens. In this work we identify sRNAs in the Gram positive opportunistic pathogen Enterococcus faecalis. We characterized 11 sRNAs by tiling microarray analysis, 5′ and 3′ RACE-PCR, and Northern blot analysis. Six sRNAs were specifically expressed at exponential phase, two sRNAs were observed at stationary phase, and three were detected during both phases. Searches of putative functions revealed that three of them (EFA0080_EFA0081 and EFB0062_EFB0063 on pTF1 and pTF2 plasmids, respectively, and EF0408_EF04092 located on the chromosome) are similar to antisense RNA involved in plasmid addiction modules. Moreover, EF1097_EF1098 shares strong homologies with tmRNA (bi-functional RNA acting as both a tRNA and an mRNA) and EF2205_EF2206 appears homologous to 4.5S RNA member of the Signal Recognition Particle (SRP) ribonucleoprotein complex. In addition, proteomic analysis of the ΔEF3314_EF3315 sRNA mutant suggests that it may be involved in the turnover of some abundant proteins. The expression patterns of these transcripts were evaluated by tiling array hybridizations performed with samples from cells grown under eleven different conditions some of which may be encountered during infection. Finally, distribution of these sRNAs among genome sequences of 54 E. faecalis strains was assessed. This is the first experimental genome-wide identification of sRNAs in E. faecalis and provides impetus to the understanding of gene regulation in this important human pathogen
Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors
Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% Gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence
Global metabolic response of Enterococcus faecalis to oxygen
Oxygen and oxidative stress have become relevant components in clarifying the mechanism that weakens bacterial cells in parallel to the mode of action of bactericidal antibiotics. Given the importance of oxidative stress in the overall defense mechanism of bacteria and their apparent role in the antimicrobial mode of action, it is important to understand how bacteria respond to this stress at a metabolic level. The aim of this study was to determine the impact of oxygen on the metabolism of the facultative anaerobe Enterococcus faecalis using continuous culture, metabolomics and 13C-enrichment of metabolic intermediates. When E. faecalis was rapidly transitioned from anaerobic to aerobic growth, cellular metabolism was directed towards intracellular glutathione production and glycolysis was upregulated two-fold, which increased the supply of critical metabolite precursors (e.g. glycine and glutamate) for sulfur metabolism and glutathione biosynthesis as well as reducing power for cellular respiration in the presence of haemin. The ultimate metabolic response of E. faecalis to an aerobic environment was the upregulation of fatty acid metabolism and benzoate degradation, which was linked to important changes in the bacterial membrane composition as evidenced by changes in membrane fatty acid composition and the reduction of membrane-associated demethylmenaquinone. These key metabolic pathways associated with the response of E. faecalis to oxygen may represent potential new targets to increase the susceptibility of this bacterium to bactericidal drugs.This work was funded by the HRC (Health and Research Council of New Zealand) and the FCT (Portuguese Foundation for Science and Technology), with grant reference SFRH/BD/47016/2008
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